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Background: Immune checkpoint inhibitors (ICIs) represent an effective cancer immunotherapy yet are associated with immune-related adverse events (irAEs). The aim of this study was to characterize irAEs involving the peripheral nervous system (PNS-irAEs) in a real-world cohort of ICI-treated patients. Methods: Cancer patients treated with ICIs between January 2014 and March 2022 were included. Patients with PNS-irAEs were identified and divided into two groups: (1) cranial/peripheral neuropathies and (2) myasthenia gravis (MG) and/or myositis. Clinical characteristics and outcomes, measured with the modified Rankin Scale (mRS), were compared among the two groups. Results: Among 920 ICI-treated patients, 20 patients (2.17%) developed a PNS-irAEs. The median latency from ICI exposure was 8.8 weeks and the median time from onset to clinical nadir was 3.5 weeks. Eleven patients developed a neuropathy: polyneuropathy (n = 4), cranial neuropathy (n = 3), small-fiber neuropathy (n = 3), brachial plexopathy (n = 1). Nine patients presented MG and/or myositis: concomitant MG and myositis (n = 6), isolated myositis (n = 2), exacerbation of MG (n = 1). Immunosuppressive treatment and/or ICI withdrawal determined a significant clinical improvement, expressed by a mRS reduction, in the neuropathy group (p = 0.004), but not in the MG/myositis group (p = 0.11). Overall, death due to irAEs occurred in four patients (20%), all with MG/myositis. Compared to patients with neuropathies, those with MG/myositis had a shorter latency onset (p = 0.036), developed more frequently concomitant non-neurologic irAEs (p = 0.028) and showed a higher mortality rate (p = 0.026). Conclusions: In our large cohort of ICI-treated patients, 2.17% developed PNS-irAEs. Compared to ir-neuropathies, ir-MG/myositis tend to occur earlier from ICI exposure and present a worse response to treatment and a higher mortality. [ABSTRACT FROM AUTHOR]

Objectives: This work aimed to report the demographic and clinical characteristics of two new cases with non-paraneoplastic anti-Hu-associated gut motility impairment, and perform a thorough revision covering anti-Hu-associated paraneoplastic (PGID) and non-paraneoplastic (nPGID) gastrointestinal dysmotility. Background: Several case series have clearly established a relationship between certain type of cancers, the development of circulating anti-Hu antibodies, and the concomitant usually severe gastrointestinal dysmotility; in contrast, a few studies focused on anti-Hu-associated nPGID. Methods: We searched for studies regarding anti-Hu-associated gastrointestinal manifestations and extracted data concerning clinical characteristics of patients, including specific demographic, oncological, neurological, gastrointestinal, histological, and treatment response features. Results: Forty-nine articles with a total of 59 cases of anti-Hu-associated gastrointestinal dysmotility were analyzed. The patients' age at symptom onset significantly differed between PGID and nPGID (median 61 vs 31 years, p < 0.001). Most cancers (95%) in PGID were detected within 24 months from the beginning of gastrointestinal symptoms. The impairment of gastrointestinal motility was generalized (i.e., involving the whole gut) in 59.3% of patients, with no significant differences between PGID vs nPGID group. nPGID patients showed a better response to immunomodulatory/immunosuppressive treatment and a longer life expectancy. Conclusions: Anti-Hu-associated gastrointestinal dysmotility covers a wide clinical spectrum. Patients with otherwise unexplained gastrointestinal dysmotility, especially when associated with other neurological symptoms, should be tested for anti-Hu antibodies regardless age of onset and disease duration. Compared to PGID, nPGID occurs in younger patients with a long duration of disease. [ABSTRACT FROM AUTHOR]

A number of cortical and spinal excitability variables have been tested in a patient with Stiff Person Syndrome (SPS), before and after immunotherapy with mycophenolate mofetil, intravenous immunoglobulin and corticosteroids, which normalized plasma levels of anti-GAD antibodies and dramatically improved the clinical picture. The overlapping time-course of neurophysiological, clinical and bio-umoral findings suggests that immunotherapy might have changed GABA/Glutamate balance at cortical level, favoring the former, as reflected by normalization of the startle reflex, lengthening of the cortical silent period and clear-cut reduction of intracortical facilitation to paired-pulse transcranial magnetic stimulation. This represents the first report investigating effects of immunotherapy on cortical excitability in SPS. [ABSTRACT FROM AUTHOR]

Background:. Idiopathic hypertrophic cranial pachymeningitis (IHCP) is a rare, poorly understood, inflammatory disease, usually involving the dura mater of skull base, tentorium, and falx, and presenting with headache, progressive cranial nerve palsies, and cerebellar dysfunction. Patients and Methods:. In four patients, the diagnosis of IHCP has been made on the basis of extensive clinical, and radiological investigation, and confirmed by dural biopsy in three patients. The clinical follow-up ranges from 24 to 120 months. Results :. At diagnosis, all the patients complained of severe, progressively increasing headache, two had simple or complex partial seizures, but none had cranial nerve palsies. Two patients had electrophysiological evidence of axonal peripheral neuropathy, biopsy-proved in one of them. In all the patients, MRI showed linear or focal thickening of the dura mater of the tentorium and/or of the convexity, sparing the skull base. In one patient, MRI findings resembled chronic subdural hematoma. Dural biopsy demonstrated fibrosis and prominent CD4+ T-cells inflammatory infiltrate. Pachymeningitis was highly responsive to steroid therapy, as was the peripheral neuropathy. In three patients, temporary steroids withdrawal led to dramatic clinical worsening including status epilepticus in one. Conclusions :. In the patients here reported, absence of cranial nerve impairment, seizures, MRI findings resembling chronic subdural hematoma, and association with polineuropathy were unusual findings of IHCP. Moreover, the type of inflammatory infiltrate, lacking in previous reported cases, suggests a probable pathogenetic role for cell-mediated immunity of unknown origin. [ABSTRACT FROM AUTHOR]

Objective: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. Methods: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. Results: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081–21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. Conclusions: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis. [ABSTRACT FROM AUTHOR]

A few patients presenting with autoimmune encephalitis following COVID-19 vaccinations were reported, including a case diagnosed with anti-LGI1 encephalitis [[2]-[4]]. Even though this epidemiological data should be considered cautiously, the presence of a strict temporal relationship between disease onset and vaccination lets us hypothesize that anti-LGI1 encephalitis may represent a rare complication of COVID-19 vaccination. [Extracted from the article]

Background: If Parkinson's Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD patients. Objective: In the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine. Method: A case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored. Results: Out of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (p < 0.001) and diabetes (p = 0.049) compared to non-COVID-19. In non-COVID-19 PD population (n = 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases. Conclusion: A higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor of the "Journal of Neurology" about the clinical evidence of fluconazole-induced carbamazepine toxicity.